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Adrian Wills

Publications and source records attributed to Adrian Wills.

6 recordsLinked to original sources
PubMed2006

Clinical features and natural history of neuroferritinopathy caused by the FTL1 460InsA mutation.

Neuroferritinopathy is a progressive potentially treatable adult-onset movement disorder caused by mutations in the ferritin light chain gene (FTL1). Features overlap with common extrapyramidal disorders: idiopathic torsion dystonia, idiopathic Parkinson's disease and Huntington's disease, but the phenotype and natural history have not been defined. We studied a genetically homogeneous group of 41 subjects with the 460InsA mutation in FTL1, documenting the presentation, clinical course, biochemistry and neuroimaging. The mean age of onset was 39.4 years (SD = 13.3, range 13-63), beginning with chorea in 50%, focal lower limb dystonia in 42.5% and parkinsonism in 7.5%. The majority reported a family history of a movement disorder often misdiagnosed as Huntington's disease. The disease progressed relentlessly, becoming generalized over a 5-10 year period, eventually leading to aphonia, dysphagia and severe motor disability with subcortical/frontal cognitive dysfunction as a late feature. A characteristic action-specific facial dystonia was common (65%), and in 63% there was asymmetry throughout the disease course. Serum ferritin levels were low in the majority of males and post-menopausal females, but within normal limits for pre-menopausal females. MR brain imaging was abnormal on all affected individuals and one presymptomatic carrier. In conclusion, isolated parkinsonism is unusual in neuroferritinopathy, and unlike Huntington's disease, cognitive changes are absent or subtle in the early stages. Depressed serum ferritin is common and provides a useful screening test in routine practice, and gradient echo brain MRI will identify all symptomatic cases.

Adolescent↗
PubMed2005

Gluten Ataxia and Post-Streptococcal Central Nervous System Syndromes: Emerging Immune-mediated Disorders of the Central Nervous System?

There is an "emerging concept" that central nervous system dysfunction can be caused by an aberrant immune response triggered by exogenous antigens such as the food allergen gluten or streptococcal infection. The hypothesis of a gluten sensitive ataxia remains unproven, but is worthy of consideration. The data in support of this hypothesis require critical review before any treatment recommendations can be formulated. The idea that anti-gliadin antibody seropositivity per se justifies the term "gluten sensitivity" is important because it offers potential therapeutic possibilities, including simple exclusion diets, for patients with anti-gliadin antibody-associated ataxia. Post-streptococcal basal ganglia dysfunction has various manifestations, all of which fall into a relatively well-defined symptom complex or syndrome. Anti-basal ganglia antibodies that are associated with serologic evidence of recent streptococcal infection are a potential diagnostic marker for this group of disorders, which includes Sydenham's chorea (SC) as the prototype. More recently subjects with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, Tourette's syndrome, obsessive-compulsive disorder and other movement disorders have been described in association with anti-basal ganglia antibodies. The apparent overlap between the clinical phenotype of SC, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, Tourette's syndrome, and obsessive-compulsive disorder suggests that they may represent one disease entity. The current working hypothesis is that antibodies induced in response to streptococcal infection cross-react with antigenic determinants in the basal ganglia resulting in basal ganglia dysfunction. Although the experimental evidence is incomplete, there is sufficient evidence to support immune-mediated basal ganglia dysfunction as an emerging clinical entity. This has important implications for the diagnosis and treatment of subjects with these disorders. The latter includes the judicious use of antibiotic prophylaxis and immunomodulatory therapies. Apart from the diagnosis and management of SC, no consensus exists regarding the diagnosis and management of the other clinical entities within this group of disorders.

Journal Article↗
PubMed2004

A clinical, genetic and candidate gene study of Silver syndrome, a complicated form of hereditary spastic paraplegia.

Silver syndrome (SS) is a complicated form of hereditary spastic paraplegia associated with distal wasting of the small muscles of the hands. We have previously described a large kindred with SS and mapped a genetic locus (SPG17) to chromosome 11q12-q14. In the current study we analyse the clinical phenotype and perform linkage analysis in three new SS families. In addition we analyse candidate genes mapping to the SS locus (SPG17). Clinical assessments were performed on 25 (15 affected) individuals from each family in which SS segregates with variable clinical expression. Neurophysiological studies, performed in the index case of two families, suggested anterior horn cell or nerve root involvement. Linkage analysis using microsatellite markers mapping to the SPG17 locus was performed and only one of the three families had a microsatellite segregation pattern compatible with linkage. Candidate genes mapping to the SS critical region were analysed in this and one other SPG17-linked family. Mutation analysis of genes encoding calpain 1 ( CAPN1), copper chaperone for superoxide dismutase ( CCS), ADP ribosylation factor-like 2 ( ARL2), LOC120664, a putative homologue of atlastin ( ATLSTL-1) and sorting nexin 15 ( SNX15) failed to identify any disease-specific mutations. SS therefore exhibits both clinical and genetic heterogeneity and the SPG17 locus may account for a significant proportion of SS mutations in the UK.

Adolescent↗
PubMed2003

[123I]-FP-CIT-SPECT demonstrates dopaminergic deficit in orthostatic tremor.

There is increasing evidence of a potential role of the dopaminergic system in orthostatic tremor (OT): Association with parkinsonism and treatment effects of L-dopa and dopamine agonists have been reported. Eleven patients with isolated OT had single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123)I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) as dopamine transporter tracer. Results were compared with 12 age-matched normal controls and 12 patients with Parkinson's disease (PD). A marked reduction in striatal tracer binding was found in OT compared to normal controls (p < 0.001). Tracer uptake was significantly higher and more symmetrical than in PD, and caudate and putamen were equally affected. L-dopa challenges, performed in seven patients, showed a small but non-significant improvement on EMG and a small but significant improvement in clinical parameters on blinded video rating. Two-month open-label L-dopa treatment (600 mg/day) led to a small improvement in two of five patients but no significant overall change. Olfactory function on University of Pennsylvania Smell Identification Test was normal. Our finding of a marked tracer uptake reduction on dopamine transporter SPECT supports a role of the dopaminergic system in OT. Lack of evidence of a clinically relevant therapeutic response to L-dopa suggests that other mechanisms must also be involved in the pathogenesis.

Aged↗